Hypofractionated, 3-week, Preoperative Proton or X-ray Radiotherapy for Patients With Localized Soft Tissue Sarcoma

Official title

PROSARC-1. Hypofractionated, 3-week, Preoperative Proton or X-ray Radiotherapy for Patients With Localized Soft Tissue Sarcoma. A Single-arm, Multicenter, Phase II Clinical Trial.

Overview

The purpose of the study is to investigate whether a personalized selection of patients with localized soft tissue sarcoma for preoperative proton radiation therapy can reduce long-term radiation side effects without increasing surgical complications or reducing the effectiveness of the treatment. Two radiation plans will be created for each patient-one for protons and one for photons-and through a national meeting, we will determine which type of radiation therapy each patient will receive. The radiation dose will be the same for both photons and protons. The primary endpoint is surgical complications 120 days after surgery. Secondary endpoints include overall survival, local recurrence-free survival, disease-free survival, side effects, and quality of life. Furthermore, the study will investigate biomarkers that may predict response to radiation therapy, including changes in the tumor's genetic material (DNA), measurement of various molecules in the bloodstream, and the tumor's appearance on MRI scans. The study will be conducted in Norway, with a planned inclusion of 110 patients.

Detailed description

The objective of the PROSARC-1 trial is to investigate whether a national personalized approach with proton beam therapy (PBT) to selected soft tissue sarcoma (STS) patients can reduce long-term toxicity without increasing surgical complications or compromising local control. PROSARC-1 is a single arm, open-label, multicenter phase II trial initiated at Department of Oncology, Oslo University Hospital (OUS). The main inclusion criterion is patients with newly diagnosed STS of the head, neck, extremity or trunk wall. The primary endpoint is major wound complications (MVC) occurring within the first 120 days after surgery. We expect to include 110 patients over three years and all patients will be followed for up to five years. All the sarcoma centers in Norway participate in the study: OUS; Haukeland University hospital (HUH); St Olavs Hospital (SOH) and the University Hospital of North-Norway (UNN). The indication for preoperative radiotherapy (RT) will be decided in the sarcoma multidisciplinary (MDT) meeting at each center. For included patients, one X-ray radiotherapy (XRT) and one PBT plan will be made for comparison. A weekly national sarcoma radiotherapy meeting will compare the plans and recommend XRT or PBT treatment based on a careful clinical evaluation, also considering thresholds based on the toxicity grade. The prescribed dose is standard 42.75 Gy in 15 fractions over 3 weeks for both XRT and PBT.

The PROSARC-1 trial includes translational radiomic research, where we aim to elucidate underlying mechanisms related to radiotherapy effect. To facilitate future biomarker studies for personalized therapy we will collect excess tumor tissue, whole blood, plasma and serum.

Interventions

• Radiation preoperative
  The radiotherapy will be delivered 2.85 Gy x 15 for both x-ray or proton radiotherapy. A comparative doseplan will decide if the patient will receive proton og x-ray radiotherapy.
• Other Quality of life
  Questionnaire
• Other Functional outcome
  Questionnaire

Primary outcome measures

• Major surgical complications [Time frame: 120 days from surgery]

Secondary outcome measures (8)

• Local recurrence-free survival [Time frame: Up to five years after radiation therapy.]
• Disease-free survival [Time frame: Up to five years after radiation therapy]
• Overall survival [Time frame: Up to five years after radiation therapy]
• Overall response rate, defined as partial or complete response using RECIST v1.1 [Time frame: Up to five years after radiation therapy]
• Pathological response [Time frame: Perioperative]
• Health-related quality of life [Time frame: Up to five years after radiation therapy]
• Functional outcome [Time frame: Up to five years after radiation therapy]
• Functional outcome [Time frame: Up to five years after radiation therapy]

Eligibility criteria

Inclusion criteria

• ≥ 18 years of age at the time of informed consent.
• Histological diagnosis of STS, except rhabdomyosarcoma and Ewing sarcoma. Pleomorphic rhabdomyosarcomas are eligible.
• Primary tumor localized in head, neck, extremity, girdle and/or trunk wall.
• Measurable disease according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Before patient registration, written informed consent must be given according to national and local regulations.
• Ability to fill in patient questionnaires and comply with study procedures, including travelling to Bergen or Oslo for PBT.

Exclusion criteria

• Locoregional or distant metastasis as assessed by CT and/or MRI at time of diagnosis. Patients with lung nodules <10 mm of uncertain etiology may be included.
• Prior or concurrent malignant disease whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible. Patients with a history of breast cancer, requiring continued hormonal treatment (e.g. anti-estrogen or an aromatase inhibitor) may be included. Patients with a history of prostate cancer, requiring continued support with luteinizing hormone releasing hormone (LHRH) agonists, with or without androgens, may be included.
• Previous radiotherapy to the primary tumor region.
• Patients with pacemakers and/or implanted defibrillators.
• Administration of systemic cancer therapy (i.e. chemotherapy, targeted therapy or immune therapy) within 14 days prior to the first fraction of radiotherapy.
• Patients not able to give an informed consent or comply with study regulations as deemed by study investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Norway · 4 centers

• Haukeland University Hospital — Bergen
• Oslo University Hospital — Oslo
• University Hospital of North Norway — Tromsø
• St. Olavs University Hospital — Trondheim

Identifiers

NCT: NCT07169344 · 915811

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗